The ultimate embodiment of an extracorporeal closed-loop blood-glucose control system will be a portable de- vice consisting of three components: a continuous glucose monitor (CGM), a continuous subcutaneous (SC) drug infusion device (e.g. an insulin pump), and a control algorithm. The control algorithm links the other two com- ponents by receiving the glucose data stream from the CGM, making a therapeutic decision based on that data stream, and issuing commands to the drug infusion device. We have designed and tested closed-loop control systems that safely and effectively regulate blood-glucose (BG) levels based on either a venous BG data stream (in diabetic pigs and in people with type 1 diabetes) or a CGM data stream (in diabetic pigs). We have further tested our CGM-based closed-loop control system in diabetic pigs using both an insulin-only configuration and a bihormonal (insulin and glucagon) configuration. Based on our positive preclinical results, we hypothesize that our CGM-based closed-loop glucose-control system can provide safe and effective BG control in people with type 1 diabetes. Our objective is to test this hypothesis and optimize our closed-loop system by conducting human trials in the Mallinckrodt Clinical Research Center at the Massachusetts General Hospital on healthy adult vol- unteers (18 years and older) with type 1 diabetes. We propose to achieve this objective with the following three specific aims: (1) to test the safety and efficacy of our control system (in both the bihormonal and insulin-only configurations) in regulating BG in adults with type 1 diabetes based on interstitial-fluid (ISF) glucose data from a CGM, (2) to repeat the study of Aim 1 using the same control system with the addition of periods of structured exercise in the study protocol, and (3) to conduct 5-day continuous closed-loop in-patient studies using a fully integrated PDA-based portable control system in adults with type 1 diabetes.